Abstract: Objective Hepatocellular carcinoma （HCC） is one of the most common malignant tumors with poor prognosis and high recurrence rate. Ferroptosis is a recently discovered form of iron-dependent programmed cell death, which is different from cell necrosis, apoptosis, and autophagy and is driven by lipid peroxidation. This study explored the relationship between ferroptosis-related genes with prognosis in HCC patients. Methods Gene expression and corresponding clinicopathological data of HCC patients were downloaded from public databases. Univariate COX regression analysis was used to screen out prognostic ferroptosis-related genes, and Lasso COX regression analysis was used to construct a prognostic model. Multivariate COX regression analysis was used to confirm that the prognostic model was an independent risk factor. Finally, functional analyses were performed using Genome Ontology （GO）, Kyoto Genome Encyclopedia （KEGG）, and Single Sample Gene Enrichment Analysis （ssGSEA）. Results Univariate Cox regression analysis showed that 16 ferroptosis-related genes were significantly associated with prognosis （P<0.0001）. Using Lasso Cox regression analysis, we eventually constructed a prognostic model based on 10 ferroptosis-related genes. All patients in the cohort were divided into high-risk group and low-risk group according to the median of riskScore （Calculated by prognostic model）. The survival rate of patients with HCC in the high-risk group was lower and the survival time was shorter （P<0.05）. Multivariate Cox regression analysis showed that riskScore was an independent prognostic factor for patients with HCC （P<0.001）. In addition, functional analyses revealed significant differences in the immune microenvironment between the high-risk and low-risk groups. Conclusion In this study, a prognostic model based on 10 ferroptosis death-related genes was established and verified as an independent prognostic factor in patients with HCC, which provides a reference for the prognosis of patients with HCC.

Key words: hepatocellular carcinoma, ferroptosis, prognosis

摘要： 目的 肝细胞癌是最常见的恶性肿瘤之一,具有预后差、复发率高的特点。铁死亡是最近发现的一种铁依赖性的细胞程序性死亡的形式,不同于细胞坏死、细胞凋亡、细胞自噬,由脂质过氧化驱动。该研究探讨了铁死亡相关基因与肝细胞癌患者预后之间的关系。方法 从公共数据库中下载肝细胞癌患者的基因表达及相应的临床病理数据。使用单因素COX回归分析筛选预后相关的铁死亡相关基因,利用LASSO COX回归分析构建预后模型。多因素COX回归分析用于确认预后模型为独立的风险因素。最后,使用基因本体（GO）、京都基因组基因百科全书（KEGG）和单样本基因富集分析（ssGSEA）来进行功能性分析。结果 通过单因素COX回归分析,确认了16个与预后显著相关的铁死亡相关基因（P < 0.0001）。利用LASSO COX回归分析,我们最终构建了一个基于10个铁死亡相关基因的预后模型。将队列中所有患者根据模型计算分为高风险组和低风险组,高风险组的肝细胞癌患者生存率较低,生存时间较短（P < 0.05）。多因素COX回归分析显示,风险评分是肝细胞癌患者的独立预后因素（P < 0.001）。此外,功能性分析显示,高风险组与低风险组之间的免疫微环境存在显著差异。结论 本研究构建了基于10个铁死亡相关基因的预后模型,并且验证了该模型为肝细胞癌患者的独立预后因素,这为肝细胞癌患者的预后提供了参考。

关键词: 肝细胞癌, 铁死亡, 预后